Impact of the Systemic Inflammatory Indices on Birth Weight: A Prospective Observational Study

Several studies explored the role of maternal systemic inflammation indices during pregnancy. Different conditions, such as gestational hypertension, preeclampsia, and gestational diabetes, are associated with abnormal systemic inflammation indices. However, there is a lack of research on the impact of systemic inflammation indices on fetal growth in physiological pregnancies. The objective of this study was to explore the potential associations between birth weight, length, and head circumference with a group of systemic inflammatory indices, namely, platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR), the mean platelet volume-to-lymphocyte ratio (MPVLR), monocyte-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI).

Full-term, physiological pregnancies admitted to a tertiary center from November 2019 until February 2021 were included in a prospective observational study. We excluded pregnancies affected by gestational or pregestational diabetes, chronic hypertension, gestational hypertension, pre-eclampsia/eclampsia, fetal growth restriction, preterm delivery or premature rupture of membranes, multiple pregnancies, and malformed fetuses. Sociodemographic characteristics, clinical data, and complete blood count were recorded.

Continuous variables were reported as either the means and standard deviation or median and interquartile ranges according to their distribution, as assessed by the Shapiro-Wilk normality test. Categorical variables were reported as percentages. To measure the linear association between continuous variables, the Pearson correlation test was used if variables had a normal distribution. Otherwise, Spearman's rank correlation test was calculated. To obtain an inflammatory latent score, a principal component analysis (PCA) was performed on NLR, PLR, MPVLR, MLR, SII, and SIRI.

Overall, 264 pregnant women came to our observation before the delivery. After the exclusion criteria, 199 pregnant were included. The Spearman's rank correlation test showed a high correlation among the indices. Then, a PCA was performed to a composite indicator of inflammatory score. The first principal component was selected, with a proportion of explained variance equal to 73.11%. The contributions of variables suggested excluding from the score the MLR index. From the linear regression models, results denoted that the inflammatory score negatively affects the birth weight (β = -42.60, 95% CI -76.91, -8.28) and the head circumference (β = -0.14, 95% CI -0.24, -0.04); however, the effect of the score on the birth length is not statistically significant at 5% (β = -0.12, 95% CI -0.27, 0.02).

This research's main limitation is the lack of data about the indirect inflammatory markers during the first and second trimesters of pregnancy. In addition, no neonatal outcomes were scheduled, such as NICU hospitalization for the different neonatal pathologies.

The results of our study revealed a negative direct correlation between the composite indicator of inflammatory score and the birth weight and fetal head circumference. This novel finding prompts further evaluation of the role of indirect inflammatory markers on fetal growth and neonatal outcomes and highlights the need for additional research to clarify the complex relationship between inflammation and pregnancy.